PROJECT SUMMARY/ABSTRACT BACKGROUND. Vaso-occlusive pain crises (VOC) are the most common complication in youth with sickle cell disease (SCD) and comprise the leading cause of healthcare utilization. Adolescents with (SCD) are at-risk for experiencing VOCs that may result in vascular and nervous system damage, sensitize neuromodulatory pain circuits, and ultimately affect future pain symptomatology. Stress and pain itself have been cited as potential triggers for VOC and are also associated with physiological stress responses that alter autonomic nervous system (ANS) function. Such ANS changes can lead to vasoconstriction, resulting in reduced peripheral blood flow, further occlusion of SCD red blood cells, and VOC. Social stress has also been linked to maladaptive physiological stress responses and recent data indicate that perceived SCD-related stigma is associated with negative psychosocial and medical outcomes in adolescents. Neuromodulatory interventions (e.g., hypnosis) may represent a promising approach to pain management for youth with SCD. Hypnosis has been shown to reduce activity in supraspinal areas identified as components of the ?pain matrix? as well as increase temperature in the extremities, which may affect autonomic responses and vasodilation. Despite preliminary support for the positive effects of hypnosis on pain outcomes in SCD, no laboratory-based studies exist with pediatric SCD samples and no existing studies have examined how perceived SCD-related stigma may moderate acute pain responses in youth with SCD. Such work may elucidate potential mechanisms underpinning VOC and identify new targets for intervention. SPECIFIC AIMS. This proposal will utilize psychophysiological biomarkers of pain and peripheral vascular reactivity to test the effects of a laboratory- based hypnosis session on peripheral blood flow and acute pain and autonomic responses in adolescents with SCD and healthy controls, and examine how perceived SCD-related stigma may moderate acute pain responses. METHODS. A quasi-experimental, correlational design will be conducted. Three laboratory thermal heat pain tasks will be completed before and during a 30-minute hypnosis session. Peripheral blood flow, pain tolerance, threshold and intensity, heart rate variability, skin conductance response, and SCD- related stigma will be assessed. GOALS. To gain advanced training in laboratory-based methodology and physiological analyses to foster a deeper understanding of the potential mechanisms underlying the experience of pain in SCD, and ultimately conduct cutting-edge clinical research that examines the interface between physiological and psychological models of pain and emotion in vulnerable populations such as youth living with SCD .